1. Field of the Invention
This invention relates to a method for administering Photodynamic Therapy to a highly vascularized tissue.
2. Prior Art
Photodynamic Therapy, PDT, is the treatment of diseased, usually hyper proliferative tissue using photosensitizing chemicals and light. PDT, as presently used, is based on the observation that certain photosensitizing compounds preferentially concentrate in hyperproliferating tissue relative to most other normal tissues. A well known example of a procedure which exploits this differential concentration of photosensitizer is the use of PDT to treat tumors. This preferential concentration, or therapeutic ratio as it is sometimes called, is the basis of obtaining the potential therapeutic selectivity that is usually desired in the clinical application of PDT. This is generally obtained by first administering the photosensitizer by a suitable route, generally intravenously, then waiting for some period of time for the photosensitizer to be accumulated within the target tissues while most nontarget tissue eliminate the photosensitizer. The reason for this selective affinity and retention of photosensitizers in hyperproliferating tissue is not presently known but support for the observation has been documented for a variety of photosensitizers and hyperproliferating tissue.
In most cases, the therapeutic response of PDT includes both cellular and vascular effects. PDT, in accordance with current clinical practice, requires the procedural step of allowing a period of time to elapse after injection of a photosensitizer into the blood stream to permit the photosensitizers to accumulate in a tissue. The countdown, the elapsed time required for accumulation prior to administering phototherapeutic light, begins upon introduction of the photodynamically active photosensitizer into the patient's circulatory system. With time, the photosensitizer is taken up by tissue(s) and tissue components and bound thereto. While utilization of this preferential, differentially selective photosensitizer uptake/retention by hyperproliferating tissue is effective for a variety of photosensitizers and target tissues, due to uptake throughout the body and elimination, the delay time necessary for the accumulation of a therapeutically effective concentration of photosensitizer in the tissue generally requires the use of a relatively high photosensitizer dose. This high level of drug, in turn, can lead to problems such as systemic and local toxicity and prolonged photosensitivity of the skin. In addition, this methodology does not specifically target vasculature but focuses instead on the selective ability of a target tissue (a tissue to be treated by PDT), to take up and retain photosensitizers from the blood.
In summary, in the art, PDT is generally used to treat hyperproliferating tissues, i.e. cancer, by first administering a photosensitizer to the patient by a suitable route such as by intravenous [IV], intramuscular [IM], intraperitoneal [IP] injection or oral administration, and then waiting for a predetermined period of time known, a priori to be sufficient to effect the preferential uptake and retention of the photosensitizer in the target tissue relative to the concentration of the photosensitizer in normal (non-hyperproliferating) tissues. By permitting time to elapse after systemic administration of the drug, the photosensitizer is generally localized in a variety of tissue/cell types as well as locations within the target tissue. The time for photosensitizer build-up in a target tissue varies but is in the range of 2-24 h. The resulting therapeutic response therefore generally involves a variety of cytological effects.
A recent exception to the procedure summarized above is the use of PDT to treat the retinal neovasculature related to a form of Age Related Macular Degeneration. In this therapeutic procedure, the photosensitizer is administered IV and the therapeutic light is applied selectively to the neovascular area within the eye a short time afterward. The leakiness of the vasculature due to the fragile and permeable nature of the neovasculature in the eye, causes a large quantity of fluid to pool in the immediate vicinity of the neovasculature. The pooled, localized extravascular fluid contains a significant amount of photosensitizer. Upon photoactivation, tissue destruction within the neovascular area is enhanced due to the abundance of the photosensitizer therewithin relative to the neighboring tissue which lacks such neovasculature and the concomitant accumulation of fluid therearound.